Integrin alpha(IIb)beta3 signals lead cofilin to accelerate platelet actin dynamics |
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Authors: | Falet Hervé Chang Gregory Brohard-Bohn Brigitte Rendu Francine Hartwig John H |
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Affiliation: | Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, One Blackfan Circle, Karp 6, Boston, Massachusetts 02115, USA. hfalet@rics.bwh.harvard.edu |
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Abstract: | Cofilin, in its Ser3 dephosphorylated form, accelerates actin filament turnover in cells. We report here the role of cofilin in platelet actin assembly. Cofilin is primarily phosphorylated in the resting platelet as evidenced by a specific antibody directed against its Ser3 phosphorylated form. After stimulation with thrombin under nonstirring conditions, cofilin is reversibly dephosphorylated and transiently incorporates into the actin cytoskeleton. Its dephosphorylation is maximal 12 min after platelet stimulation, shortly after the peak of actin assembly occurs. Cofilin rephosphorylation begins 2 min after activation and exceeds resting levels by 510 min. Cofilin is dephosphorylated with identical kinetics but fails to become rephosphorylated when platelets are stimulated under stirring conditions. Cofilin is normally rephosphorylated when platelets are stimulated in the presence of Arg-Gly-Asp-Ser (RGDS) peptide or wortmannin to block IIb3 cross-linking and signaling or in platelets isolated from a patient with Glanzmann thrombasthenia, which express only 23% of normal IIb3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation in the platelet actin cytoskeleton are decreased when IIb3 is engaged. Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets. |
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